I've been tossing around some thoughts about the mechanism for controlling gout with allopurinol and Uloric. I was trying to envision a “grand scheme” but there are just too many loose ends to tie up in my head. So I thought I'd just begin typing and maybe grow some kind of logical picture EVENTUALLY. Once it's written down I don't have to rethink THAT part (if that makes any sense.)

So we know that gout originates from either an over-production or underexcretion of uruc acid/uriate. The body makes uric acid from the oxidation of purines, proteinaceous foods that contain a xanthine structure, mostly hypoxanthine (purine base), xanthine and guanine,?an unbreakable pair of rings one with 5 carbons and one with 6. I say unbreakable becasue they are unbreakable by humans?most animals CAN break the rings and thus only man and dalmations form uric acid as the end product of xanthine oxidation.

In man, all the oxidation of hypoxanthine to?xanthine and then to uric acid?is accomplished by the aid of a HUGE molecule usually in the liver called xanthine oxidase (XA)?quite appropriately named, say what? The XA is a catalyst which accomplishes a reaction without actually being changed by it. The xanthines in the blood are?grabbed by XA and oxidized in the liver.

Enter allopurinol which is ALMOST a?hypoxanthine but with the slightest reshuffling of a couple atoms. It fools the XA into oxidizing IT into into oxipurinol ?all of which is tying up the xanthine oxidase and preventing some of the purines from being converted to uric acid. While the XA is being tied up,?the increased level of hypoxanthines and xanthines are being excreted by the kidneys.??Net result is a lowered serum uric acid. The products of allopurinol, hypoxanthine and xanthine are all more soluble than urate so the kidneys get rid of them while the XA is “busy” gettin fooled by allopurinol.

?

What might we deduce:

1. That the oxidation of allopurinol and oxypurinoll must be fairly slow, otherwise the XA would not be hindered from making uric acid.

2. That the supply of XA must be relatively fixed? Otherwise the body would make enough of it to counter any allopurinol.

So now we must ask, over the long haul will the body make more XA in response to years of allopurinol probably requiring increased dosing? If so, then stopping allopurinol after a long time might be disastrous for gout patients given larger amounts of XA.

?

So now, we are taking allopurinol. It lasts only a short time before it is converted by XA to oxypurinol which lasts even longer, several days??while it?is is again converted by XA to i'm not sure what,? tying up XA.

Questions:

1. Since allopurinol is changed quickly by XA, is it best to administer it slowly in multiple doses for more effect?

2. Is the oxypurinol ALWAYS tied? by XA during its lifetime or is it a fleeting contact? Or both?

?

Does it seem that the amount of XA can be a constant, can the molecule be thought of as living forever? Wouldn't reducing the amount be a nice help for gouties? What ELSE does it do. If nothing, then all we would lose without it is a paltry loss of calories from the inability to oxidize purines. I think we can all do without some of the calories from the immense quantities of SWEETBREADS that we eat. :D:D

?

(Like I said, this is a work in process?any thoughts, amplifications?or?corrections are welcome.)

?

Edit: I am thinking a reasonable first recommendation might be that since the initial tie-up between XA and allopurinol seems to go quickly, perhaps it might be wise to stagger the dose of the med for a more efficient use? Like 3 doses of 100mg. instead of all at once? I know that oxypurinol lasts longer but every little bit helps.

Does oxypurinol work for the whole time it's in our body anyway? Can it possibly tie up a molecule of XA for the whole week or so that it survives?

I have recently found out that Xanthine Oxidase is a bit of a misnomer becasuse the molecule co-exists with, and is quickly convertible to its twin, Xanthine?Dehydrogenase? so the proper term would be Xanthine Oxidoreductase…a versatile moleculse indeed, both catalyst of oxidation and reduction. It is responsible for the creation of superoxides, like peroxides….damaging molecules indeed.

So tying up this furious enzyme as much as possible?seems ?a good thing. This probably accounts for allopurinol's well demonstrated role in slowing down heart disease. Thus we well treated gouties may have the last laugh after all.

I've been tossing around some thoughts about the mechanism for controlling gout with allopurinol and Uloric. I was trying to envision a “grand scheme” but there are just too many loose ends to tie up in my head. So I thought I'd just begin typing and maybe grow some kind of logical picture EVENTUALLY. Once it's written down I don't have to rethink THAT part (if that makes any sense.)

So we know that gout originates from either an over-production or under-excretion of uruc acid/uriate. The body makes uric acid from the oxidation of purines, proteinaceous foods that contain a xanthine structure, mostly hypoxanthine (purine base), xanthine and guanine,?an unbreakable pair of rings one with 5 carbons and one with 6. I say unbreakable because they are unbreakable by humans?most animals CAN break the rings and thus only man and dalmatians form uric acid as the end product of xanthine oxidation.

In man, all the oxidation of xanthines is accomplished by the aid of a HUGE molecule usually in the liver called xanthine oxidase (XA)?quite appropriately named, say what? The XA is a catalyst which accomplishes a reaction without actually being changed by it. The xanthines in the blood are?grabbed by XA and oxidized

Enter allopurinol which is ALMOST a?hypoxanthine but with the slightest reshuffling of a couple atoms. It fools the XA into oxidizing IT into into oxipurinol ?all of which is tying up the xanthine oxidase and preventing some of the purines from being converted to uric acid. While the XA is being tied up,?the increased level of hypoxanthines and xanthines are being excreted by the kidneys.??Net result is a lowered serum uric acid. The products of allopurinol, hypoxanthine and xanthine are all more soluble than urate so the kidneys get rid of them.

?

What might we deduce:

1. That the oxidation of allopurinol and oxypurinoll must be fairly slow, otherwise the XA would not be hindered from making uric acid.

2. That the supply of XA must be relatively fixed? Otherwise the body would make enough of it to counter any allopurinol.

So now we must ask, over the long haul will the body make more XA in response to years of allopurinol probably requiring increased dosing? If so, then stopping allopurinol after a long time might be disastrous for gout patients given larger amounts of XA.

?

So now, we are taking allopurinol. It lasts only a short time before it is converted by XA to oxypurinol which lasts even longer before is is again converted by XA to oxypurinol which lasts several days, tying up XA.

Questions:

1. Since allopurinol is changed quickly by XA, is it best to administer it slowly in multiple doses for more effect?

2. Is the oxypurinol ALWAYS tied? by XA during its lifetime or is it a fleeting contact? Or both?

?

Does it seem that the amount of XA can be a constant, can the molecule be thought of as living forever? Wouldn't reducing the amount be a nice help for gouties? What ELSE does it do. If nothing, then all we would lose without it is a paltry loss of calories from the inability to oxidize purines. I think we can all do without some of the calories from the immense quantities of SWEETBREADS that we eat. :D:D

?

(Like I said, this is a work in process?any thoughts, amplifications?or?corrections are welcome.)

There you are, except for the medical/chemical terms.

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